This Genome-Wide Application Core (GWAC) will provide essential, cutting edge, genomic and genetic expertise to facilitate the translational impact of this highly integrated PPG. The overall objective of Core D is to provide: A) Well characterized sepsis-induced acute lung injury (ALI) and radiation-induced lung injury (RILI) cohorts of African- and European-Americans populations);B) Biological specimens (DNA, RNA, serum, and plasma) from two ethnic groups;C) A list of molecular signatures and novel candidate genes involved in ALI and RILI;D) A complete list of tagging single nucleotide polymorphisms (tSNPs) for each candidate gene involved in SIP biosynthetic/signaling pathway;E). Mid-throughput Affymetrix microarray techniques and genotyping services;and F). Genomic and genetic data analytical services to identify differentially regulated candidate genes and to test for association with susceptibility and severity of ALI or RILI. The GWAC Core will interact with all 4 Projects: 1) providing Project #1 the association study results involving sphingosine kinase and SIP lyase candidate genes and ALI. 2) providing Project #2 with a well characterized phenotype database and bio-bank (i.e. DNA, RNA, serum, plasma) on ALI cohort and an overall list of tSNPs selection of candidate genes involved in S1P biosynthesis/signaling pathway; genotyping services, case-control association data analysis 3) providing Project #3 with the genomic signatures on SI P or FTY720- or SEW-mediated LPS-induced ALI in human endothelial cells, as well as in genetically engineered mice (e.g. SI PI -/+, SI P3-/-) using microarray technology 4) providing Project #4 with a well characterized database and bio-bank on RILI cohort;association behween potential biomarkers in the serum/plasma level with genotype and SNP-specific association studies in RILI of the SIP biosynthetic pathway as well as molecular signatures in mouse whole lung tissue in response to radiation over time particularly focused on sphingolipids and related signaling.
Core D will facilitate translational research on Genomic assessment and Genetic analysis of total RNA from lung tissues or cell cultures of ALI and RILI. For Genetic application, GWAC will be responsible for providing investigators with a well characterized ALI and RILI bio-bank for the two etnic groups (European American and African American), a complete list of taggimng SNPs for each of the candidate gene involved in S1P biosynthesis pathway.
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